ABSTRACT Birth defects are the leading cause of infant mortality in the US. Birth defects also have enormous associated emotional and fiscal costs. The California Center's research efforts, both independently and in collaboration with other Centers for Birth Defects Research and Prevention (CBDRP) contributing to the National Birth Defects Prevention Study (NBDPS), have been at the forefront of public health birth defects research. With this new funding opportunity, our Center will further enhance scientific understanding of the potential causes of specific birth defects, which will undoubtedly have important implications for risk assessment and prevention of common, costly, and deadly malformations. In this application we propose the following aims: Aim 1. Enhance the epidemiologic public health research capacity of the Centers for Birth Defects and Research and Prevention by actively participating in the Birth Defects Study to Evaluate Pregnancy Exposures (BD-STEPS) and Aim 2. Utilize data from BD-STEPS as well as NBDPS for collaborative and local studies that will identify potential modifiable risk factors for selected birth defects to reduce the public health burden of birth defects in the US. The California Center is well-equipped to contribute to BD-STEPS - it is a world leader in birth defects epidemiology and highly experienced in the development, data collection and dissemination of information from population-based studies of birth defects, exemplified by its performance within the CBDRP and its highly innovative research portfolio. Our Center has extensive experience conducting research related to the BD- STEPS areas of focus, which include maternal chronic medical conditions, diabetes, obesity, physical activity, infertility and medication use. We have proposed several analytic inquiries, complemented by the use of additional innovative datasets and analytic approaches, which will enable us to collaboratively continue elucidating the contribution of these and other modifiable risk factors to birth defects.